Project Summary/Abstract: Over 2 million Americans suffer from atrial fibrillation (AF), predominantly affecting the elderly (mean age > 65 years), with over $6 billion expended annually. The three therapeutic goals of atrial fibrillation (AF) management are rhythm control, rate control, and stroke prevention. Unfortunately, standard anticoagulation therapies guided by clinical profiles are associated with non-negligible complications of major bleeding (~3% per year). This is due to the fact that currently used risk profiles are based on upstream clinical factors (age, sex, diabetes, etc.) rather than individual physiologic factors implicated in left atrium (LA) or LA appendage (LAA) thrombus formation. This high-risk, high-reward application seeks to develop a new imaging test that is needed for establishing a risk stratification system based on physiologic factors implicated in thrombus formation. The scientific premise of this study is based on a growing interest in non-invasive imaging of known parameters of atrial pathology in AF: LA/LAA volume, function, geometry, and blood stasis - one component of Virchow?s triad - as a contributor to atrial thrombus formation. This is supported by transesophageal echocardiography (TEE) studies which reported that decreased peak emptying LAA flow velocities and presence of atrial flow stasis are independent risk factors for stroke in AF. While TEE is a widely available diagnostic imaging modality to asses LA/LAA flow in AF, it has many limitations. First, TEE can only assess isolated components (e.g. peak emptying LAA flow velocities) of the 3D LA/LAA blood flow dynamics inside a complex cardiac chamber (complex LA/LAA geometry, in-flow through 4 pulmonary veins, rapid mitral-vale out flow). Second, TTE is an invasive procedure and is, therefore, associated with non-negligible complications. By leveraging an unprecedented imaging speed from compressed sensing (CS), this application seeks to further advance cardiovascular MRI and develop a 15-min MRI protocol for a comprehensive assessment of persistent and beat-to-beat variation in hemodynamics (LA and LAA flow, function, and volume) in AF. The specific objectives of this application are: (1) to combine highly-accelerated dual-venc 4D flow and real-time cine and flow MRI methods with CS, (2) to validate a new atrial MRI protocol in patient-specific models with a pulsatile flow pump in simulated regular and irregular rhythm conditions, and (3) to test whether a new atrial MRI protocol produces repeatable results in patients with AF. Unlike conventional cardiovascular MRI protocols, this rapid comprehensive atrial MRI protocol (15 min) is a major step forward in MRI technology, because it eliminates demands on patients for breath holding, improves scan efficiency, simplifies scan operation, and does not require gadolinium-based contrast agent administration. These features are important pre-requisites for a screening tool. Our proposal has high impact potential because, if successful, it will deliver a rapid, non-contrast MRI protocol for characterization of atrial hemodynamics in the complex setting of AF. The long-term clinical goal of this proposal is to personalize anticoagulation therapy and reduce the risk for bleeding in patients with AF.